{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:02:31Z","timestamp":1777705351215,"version":"3.51.4"},"reference-count":38,"publisher":"Proceedings of the National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,10,14]]},"abstract":"<jats:p>\n            Proteins, nucleic acids, and small molecules form a dense network of molecular interactions in a cell. Molecules are nodes of this network, and the interactions between them are edges. The architecture of molecular networks can reveal important principles of cellular organization and function, similarly to the way that protein structure tells us about the function and organization of a protein. Computational analysis of molecular networks has been primarily concerned with node degree [Wagner, A. &amp; Fell, D. A. (2001)\n            <jats:italic>Proc. R. Soc. London Ser. B<\/jats:italic>\n            268, 1803\u20131810; Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N. &amp; Barabasi, A. L. (2000)\n            <jats:italic>Nature<\/jats:italic>\n            407, 651\u2013654] or degree correlation [Maslov, S. &amp; Sneppen, K. (2002)\n            <jats:italic>Science<\/jats:italic>\n            296, 910\u2013913], and hence focused on\n            <jats:italic>single<\/jats:italic>\n            \/\n            <jats:italic>two-body<\/jats:italic>\n            properties of these networks. Here, by analyzing the\n            <jats:italic>multibody<\/jats:italic>\n            structure of the network of protein\u2013protein interactions, we discovered molecular modules that are densely connected within themselves but sparsely connected with the rest of the network. Comparison with experimental data and functional annotation of genes showed two types of modules: (\n            <jats:italic>i<\/jats:italic>\n            ) protein complexes (splicing machinery, transcription factors, etc.) and (\n            <jats:italic>ii<\/jats:italic>\n            ) dynamic functional units (signaling cascades, cell-cycle regulation, etc.). Discovered modules are highly statistically significant, as is evident from comparison with random graphs, and are robust to noise in the data. Our results provide strong support for the network modularity principle introduced by Hartwell\n            <jats:italic>et al.<\/jats:italic>\n            [Hartwell, L. H., Hopfield, J. J., Leibler, S. &amp; Murray, A. W. (1999)\n            <jats:italic>Nature<\/jats:italic>\n            402, C47\u2013C52], suggesting that found modules constitute the \u201cbuilding blocks\u201d of molecular networks.\n          <\/jats:p>","DOI":"10.1073\/pnas.2032324100","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T19:05:46Z","timestamp":1066158346000},"page":"12123-12128","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1139,"title":["Protein complexes and functional modules in molecular networks"],"prefix":"10.1073","volume":"100","author":[{"given":"Victor","family":"Spirin","sequence":"first","affiliation":[{"name":"Harvard\u2013MIT Division of Health Sciences and Technology, 16-343, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139"}]},{"given":"Leonid A.","family":"Mirny","sequence":"additional","affiliation":[{"name":"Harvard\u2013MIT Division of Health Sciences and Technology, 16-343, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139"}]}],"member":"341","published-online":{"date-parts":[[2003,9,29]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.292.5518.929"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.42"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.59"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35001009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061034498"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075090"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng881"},{"key":"e_1_3_2_8_2","unstructured":"Deng M. Sun F. & Chen T. (2003) Pac. Symp. Biocomput. 140\u2013151.12603024"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068664"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature750"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0735871100"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng708"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073374"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35036627"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065103"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2001.1711"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/35075138"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.298.5594.824"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00994-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.31"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/415141a"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/415180a"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.76.3251"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.210134797"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.1176"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng724"},{"key":"e_1_3_2_28_2","unstructured":"H\u00e5stad J. (1996) in Proceedings of the 37th Annual IEEE Symposium on Foundations of Computer Science (IEEE Computer Society Los Alamitos CA) pp. 627\u2013636."},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","unstructured":"Leadbetter M. R. Lindgren G. & Rootz\u03b2en H. (1983) Extremes and Related Properties of Random Sequences and Processes (Springer New York).","DOI":"10.1007\/978-1-4612-5449-2"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg054"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/46972"},{"key":"e_1_3_2_32_2","first-page":"250","volume":"1","year":"2002","unstructured":"Spruck, C. H. & Strohmaier, H. M. (2002) Cell Cycle 1, 250\u2013254.12429941","journal-title":"Cell Cycle"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.22.3967"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00008-3"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)01954-7"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.17.4954"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122653799"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202497999"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2032324100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T01:34:35Z","timestamp":1650936875000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2032324100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,29]]},"references-count":38,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2003,10,14]]}},"alternative-id":["10.1073\/pnas.2032324100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2032324100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,29]]},"assertion":[{"value":"2003-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}